In several recent studies we observed a number of behavioral and endocrinological abnormalities in the male and female offspring produced by breeding male rats, treated with morphine during adolescence, with drug-naive females. The proposed studies will continue our analysis of the paternal exposure to morphine on their progeny by examining the following: First, to completely characterize the range and magnitude of the behavioral, cognitive and physiological deficits observed in the male and female offspring of morphine-exposed fathers; second, to examine dose- and time-response considerations in these effects; and, finally, to begin to examine the mechanisms underlying the adverse effects of paternal opiate exposure on their offspring. EKC, in the presence of mu, delta and kappa1 blocking agents, labels a binding site in brain that appears a major type of opioid/opiate receptor that, heretofore, has received only limited experimental attention. We concluded that the binding site might be the epsilon receptor that was hypothesized to exist more than a decade ago. Our research program represents a continuation of our studies of the putative epsilon receptor. Our specific aims are: first, to establish whether the epsilon receptor is present in peripheral tissues and whether it is a recognition site for endogenous betaE; second, to further evaluate the possibility that the epsilon receptor in brain is a recognition site for endogenous betaE and a site through which betaE modulates pain; and, third, to solubilize, purify and characterize the epsilon receptor. The goal of this research is to characterize learning and memory deficits caused by chronic anabolic steroid exposure and to evaluate the role of anabolic steroids in analgesia. Specifically, we propose that pharmacological doses of anabolic steroids disrupt acquisition and retention of spatial tasks. We hypothesize that these learning deficits are correlated with loss of neurons in areas of hippocampus importantly involved in learning and memory. Finally, we propose that anabolic steroids enhance analgesia mediated by activation of opiate receptors and that decreased sensitivity to pain may be an important factor determining steroid abuse liability.